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A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone
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A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone
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Journal Article
A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone
2020
Overview
Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit
Aquifex aeolicus
lumazine synthase (LuS) and the 24-subunit
Helicobacter pylori
ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an
N-
linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer—stabilized in the prefusion conformation and fused with SpyCatcher—could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 µg of SARS-CoV-2 spike-LuS nanoparticle elicited similar neutralizing responses as 2.0 µg of spike, which was ~ 25-fold higher on a weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antigens
/ Aquifex
/ Bacterial Proteins - genetics
/ Betacoronavirus - isolation & purification
/ Betacoronavirus - metabolism
/ COVID-19
/ Ferritin
/ Helicobacter pylori - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Multienzyme Complexes - genetics
/ Recombinant Proteins - biosynthesis
/ Recombinant Proteins - chemistry
/ Recombinant Proteins - immunology
/ Science
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - genetics
/ Spike Glycoprotein, Coronavirus - immunology
/ Spike Glycoprotein, Coronavirus - metabolism
/ Trimers
